syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for theelicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. Weemployed online database analysis to compare the differences in the amino acid sequences of the homologousT epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and theirbinding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of allthese peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoVinfection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescentantibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive.Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restrictedimmunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with thehomologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity ofpeptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding toHLA-A2 was higher than that of other sequences. The gamma interferon (IFN-) release Elispot assay revealedthat only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-secreting T-cellresponse in HLA-A2 donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specificresponse was not observed in HLA-A2 healthy donors or in HLA-A2 donors who had been infected withSARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overtspecific T-cell response in HLA-A2 SARS-CoV-infected patients.